A Fourth Alkene Addition Pattern – Free Radical Addition

Free Radical Addition Of HBr To Alkenes With ROOR (Peroxides) 

We’ve seen that there are three major alkene reactivity patterns [carbocation, three membered ring, and concerted], but there are two minor pathways as well. This post discusses one of them: free-radical addition of HBr to alkenes, which shows the opposite regioselectivity (anti-Markovnikov) than “normal” addition of HBr to alkenes (Markovnikov) which follows the “carbocation” pathway.

Table of Contents

1. Free Radical Addition Of HBr To Alkenes Leads To “Anti-Markovnikov” Products
2. An Outline Of The Free Radical Mechanism For Addition Of HBr To Alkenes In The Presence Of Peroxides
3. Initiation Of The Free-Radical Process Through Homolytic Cleavage Of Peroxides By Heat Or Light
4. Formation Of The Bromine Radical From The Alkoxide Radical And  HBr
5. Propagation Step #1 : Addition Of Bromine Radical To The Alkene Occurs So As To Give The Most Stable Carbon Radical
6. Propagation Step #2: The Resulting Carbon Radical Removes A Hydrogen Atom From H–Br, Regenerating The Bromine Radical
7. The Termination Step
8. Summary: Free-Radical Addition Of HBr To Alkenes
9. Notes
10. Quiz Yourself!
11. (Advanced) References and Further Reading

1. Free Radical Addition Of HBr To Alkenes Leads To “Anti-Markovnikov” Products

As discussed previously, alkenes normally react with HBr to give products of “Markovnikov” addition; the bromine ends up on the most substituted carbon of the alkene, and the hydrogen ends up on the least substituted carbon. However, something interesting happens when the same reaction is performed in the presence of peroxides and  heat / light: the pattern of addition changes!

Instead of Br ending up on the most substituted carbon of the alkene, it ends up on the least. [The stereochemistry of the reaction, however, is unchanged: it still gives a mixture of “syn” and “anti” products.]

This so-called “anti-Markovnikov” addition is intriguing. What difference could the presence of peroxides, and furthermore heat (or light) make to this reaction?

2. An Outline Of The Free Radical Mechanism For Addition Of HBr To Alkenes In The Presence Of ROOR (Peroxides)

This reaction occurs through a free-radical process. (For a primer on free radical chemistry, you might want to check out this introductory article on Free Radical Reactions).  Here is an outline of the mechanism:

• Peroxides contain a weak oxygen-oxygen bond [approximately 35 kcal/mol;  compare to C-H at approx 100 kcal/mol]
• Heating leads to homolytic fragmentation of this bond – that is, the bond breaks such as to leave one unpaired electron on each atom. Strong sources of light [e.g. a floodlight or other source of light radiation which reaches into the near UV] can also serve to sever this bond.
• The resulting highly reactive alkoxy radical can then abstract a hydrogen from H-Br, giving a bromine radical. The bromine radical is the species that adds to the alkene.
• Addition to the alkene will preferably occur in such a way that the most stable free radical is formed [in the case above, the tertiary radical]. That’s why bromine ends up on the least substituted carbon of the alkene. (See: 3 Factors Which Stabilize Free Radicals)
• This tertiary radical then removes hydrogen from H-Br, liberating a bromine radical, and the cycle continues.

3. Initiation Of The Free-Radical Process Through Homolytic Cleavage Of ROOR (Peroxides) By Heat Or Light

Only a trace [catalytic] amount of peroxide is required to get the reaction started, although of course at least one molar equivalent of HBr is required to result in full addition of HBr to the alkene.

In the first step, addition of energy (in the form of heat or light) leads to homolytic fragmentation of the weak O–O bond to generate two new free radicals.  “Homolytic” means that the bond is broken such that each atom receives the same (“homos” = Greek for “same”) number of electrons.

(Most of the bond breakage we see in organic chemistry is heterolytic, where the bond breaks unequally. )

The singly barbed arrows depict the movement of single electrons; two alkoxy radicals are formed. Since there is a net increase in the number of radicals (0 →2) this is an initiation step.

Common “peroxides” for this purpose are t-butyl peroxide or benzoyl peroxide.  [Note 1]. Alternatively other free-radical “initiators” such as AIBN can also be used.

Only a catalytic amount of peroxides are used to initate this reaction (typically 10-20 mole %, although more can be used, especially when added batchwise).

4. Formation Of The Bromine Radical From The Alkoxide Radical And  HBr

In the next step, one of the oxygen radicals from step 1 removes a hydrogen from H–Br in another homolytic process.

Here, we’re forming an H–O bond (bond dissociation energy of 105 kcal/mol for H–O in t-BuO–H) and breaking an H–Br bond (bond dissociation energy of 87 kcal/mol) , so a difference in energy of about 18 kcal/mol makes this process essentially irreversible.

(Note: since this process does not change the number of free radicals, it is technically a propagation step)

5. Propagation Step #1 : Addition Of Bromine Radical To The Alkene Occurs So As To Give The Most Stable Carbon Radical

Once formed, the bromine radical can then add to the alkene.

In a relatively “flat” alkene such as 1-methylcyclohexene, addition of the radical will occur with equal probability from either face.

The question is, which atom of the double bond does the free radical attack? The bond could break two different ways, after all.

• Attack of the bromine radical on the more substituted carbon would result in a new free radical on a secondary carbon.
• Attack of the bromine radical on the less substituted carbon  would result in a new free radical on a tertiary carbon.

Free radicals are electron-deficient species and are stabilized by adjacent electron donors. The more stable free radical intermediate is the tertiary free radical, and that is why addition occurs predominantly at the less substituted carbon (i.e. the carbon attached to the fewest number of carbons).

This explains the “anti-Markovnikov” selectivity of the reaction.

6. Propagation Step #2: The Resulting Carbon Radical Removes A Hydrogen Atom From H–Br, Regenerating The Bromine Radical

In a second propagation step in the main sequence, the resulting carbon radical removes a hydrogen from another equivalent of H–Br, giving the final addition product.

Alkyl free radicals are sp²-hybridized, and are shallow pyramids that invert easily.

H–Br, therefore, can react on either face of the free radical [Note 2]. If it attacks on the same face as the Br, then we obtain a “syn” product. If it attacks on the opposite face of the Br, then the product is “anti“.

A mixture of both will be obtained. The reaction is not stereoselective. [Note 4]

A bromine radical is generated by this process, which can then add to another equivalent of alkene (propagation step #1).

7. The Termination Step

When the concentration of HBr and alkene become low relative to the concentration of free radical, termination can occur (See post: Initiation, Propagation, Termination). This could occur through a variety of specific pathways (not shown)  involving recombination of two free radicals to generate a new bond.

8. Summary: Free-Radical Addition Of HBr To Alkenes

Here are some examples [Note 3]

This reaction pathway is most commonly observed (in Org 1 and Org 2, anyway) for addition of HBr, although a rich chemistry of radical addition reactions to alkenes exists (particularly for organostannanes).

NEXT POST: Ozonolysis of Alkenes

Notes

This reaction has a considerably rich history. There was considerable controversy in the 1930’s over the addition of HBr to alkenes, with some workers reporting Markovnikov addition and others reporting the opposite. Finally, Kharasch and Mayo, using scrupulously purified HBr and allyl bromide in the dark, reproducibly obtained the Markovnikov addition product. It was found that the presence of peroxides led the reaction down a free-radical pathway, which is responsible for the “anti-Markovnikov” products found in this reaction.

H-F addition does not work due to the strength of the H-F bond.
H-Cl addition can work but the thermodynamics are not as favorable and  chain reaction is rather short. t-butylethylene is reported to give a 24% yield of primary alkyl chloride.
H-I addition has never been observed.

 Note 1. Benzoyl peroxide enjoys a common household use as an acne cleanser, and even makes an appearance in this classic ad for Oxy skin care (“Oxycute ‘Em”.)

Note 2. The geometry of free radical carbons is that of a  shallow pyramid with a low barrier for inversion, allowing for reactivity on either face. The exception is in weird cases where inversion would be highly disfavored, such as on a bridgehead (See Bicyclic Molecules and How To Name Them).

Note 3. References: 1) J. Org. Chem. 1963, 28, 2894.  2) Org. Synth. III 1955 576. 3) J. Org. Chem. 1977, 42, 1709.

Note 4. This is an oversimplification. “For our purposes” the reaction is not stereoselective. Further studies indicate that there is considerable anti selectivity for this reaction, due to a bridged bromine radical intermediate (similar to the bromonium ion that we see in bromination of alkenes). For example see Ref 5. where addition of HBr to 1-bromocyclohexene gives mostly cis-1,2-dibromocyclohexane.  For more on the bridged bromine radical, see Carey & Sundberg, Advanced Organic Chemistry A, pp 708-709. Another good reference on this is J. Am. Chem. Soc, 1973, 95, 6735. [Ref]

Quiz Yourself!

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(Advanced) References and Further Reading

Bond Dissociation Energies From Lowry & Richardson, “Mechanism and Theory In Organic Chemistry“, Harper & Row, 1987 pp 161-162 and also from this handout on Armen Zakarian’s website at UCSB.

Another source of historical context is “Free Radicals In Solution” by Cheeves Walling (1957) , p. 296-297.

1. The Peroxide Effect in the Addition of Reagents to Unsaturated Compounds and in Rearrangement Reactions.
   Frank R. Mayo and Cheves Walling
   Chemical Reviews 1940, 27 (2), 351-412
   DOI: 10.1021/cr60087a003
   F. R. Mayo was a student of the prominent chemist M. S. Kharasch, and together they first described the “peroxide effect” in the anti-Markovnikov addition of HBr to alkenes, ascribing it to a free-radical mechanism.
2. ADDITION OF HYDROGEN BROMIDE TO 4,4-DIMETHYLPENTENE-1
   M. S. Kharasch, Chester Hannum, and M. Gladstone
   Journal of the American Chemical Society 1934, 56 (1), 244-244
   DOI: 10.1021/ja01316a504
   This communication describes both products that are obtained from HBr addition to the title olefin via the electrophilic and radical mechanisms.
3. THE PHOTO-ADDITION OF HYDROGEN BROMIDE TO OLEFINIC BONDS
   WILLIAM E. VAUGHAN, FREDERICK F. RUST, and THEODORE W. EVANS
   The Journal of Organic Chemistry 1942, 07 (6), 477-490
   DOI: 10.1021/jo01200a005
   The radical addition of HBr can be initiated not just by peroxides, but also by light, as this paper describes.
4. The Peroxide Effect in the Addition of Reagents to Unsaturated Substances. XXII. The Addition of Hydrogen Bromide to Trimethylethylene, Styrene, Crotonic Acid, and Ethyl Crotonate
   Cheves Walling, M. S. Kharasch, and F. R. Mayo
   Journal of the American Chemical Society 1939, 61 (10), 2693-2696
   DOI: 10.1021/ja01265a034
   Kharasch and co-workers reported the hydrobromination of styrene in dilute pentane solution with dibenzoyl peroxide to give an 80 : 20 ratio in favor of the primary bromide. Unfortunately, detailed conditions were not provided.
5. The Stereochemistry of the Free Radical Addition of Hydrogen Bromide to 1-Bromocyclohexene and 1-Methylcyclohexene
   Harlan L. Goering, Paul I. Abell, and B. F. Aycock
   Journal of the American Chemical Society 1952 74 (14), 3588-3592
   DOI: 10.1021/ja01134a035
6. Scalable anti-Markovnikov hydrobromination of aliphatic and aromatic olefins
   Marzia Galli, Catherine J. Fletcher, Marc del Pozo, and Stephen M. Goldup
   Org. Biomol. Chem., 2016, 14, 5622-5626
   DOI: 10.1039/C6OB00692B
   This is an interesting paper demonstrating the relevance of this chemistry in modern organic synthesis; it describes the rediscovery of simple scalable conditions for synthesis of primary bromides under “initiator free” conditions from alkyl and aryl alkenes.